Pathological Findings in Congenital Diaphragmatic Hernia on necropsy
studies: A Single-Center Case Series
Chu-Yi Meng1, Ji-Zhen Zou3, Ying
Wang2, Yan-Dong Wei2, Jing-Na
Li2, Chao Liu2,
Zhong Feng2, Ling-Ling Cai3, Ping
Xiao3, Li-Shang Ma*1,2
Affiliation
1Department of Neonatal Surgery, Children’s Hospital
of Capital Institute of Pediatrics, Beijing, China.
2Department of Neonatal Surgery, Children’s Hospital
of Capital Institute of Pediatrics, Graduate School of Peking Union
Medical College, Beijing, China.
3Department of Pathology, Children’s Hospital of
Capital Institute of Pediatrics, Beijing, China.
*Correspondence to
Dr Li-Shuang Ma, Department of Neonatal Surgery, Children’s Hospital of
Capital Institute of Pediatrics, Graduate School of Peking Union Medical
College, Beijing, China;malishuang2006@126.com
Funding Information:
This work was supported by the
Pediatric Medical Coordinated
Development Center of Beijing Hospitals
Authority(XTZD20180305);Foundation project of Beijing Research
Association for Chronic Disease Prevention and Health Education in
2022(BJMB0012022028001)
* Chu-Yi Meng and Ji-Zhen Zou contributed equally to this article.
Abstract
Introduction: Congenital diaphragmatic hernia (CDH) is known with high
mortality rates and significant pulmonary morbidities. The objective of
this study was to describe the histopathological findings of necropsy
and clinical manifestations in CDH patients to find the
clinicopathological correlations.
Methods: We reviewed the postmortem findings with associated clinical
characteristics retrospectively in 8 CDH cases from 2017 to2022 July.
Results: Of the eight cases, one was bilateral congenital eventration
diagnosed by autopsy. Severe pulmonary hypertension with a right to left
shunting of large patent ductus arteriosus (PDA) obtained from
echocardiogram were most common. And the average time of survive was 46
(8-624) h. According to the autopsy reports, the major pathological lung
changes were diffuse alveolar damages (congestion and hemorrhage) and
hyaline membrane formation. Notably, although the lung volume was
significantly reduced, pulmonary structural dysplasia was not observed
at all, presented normal lung development (50%); bilateral (25%) or
ipsilateral (25%). Lobulated deformities were accompanied in three
(37.5%) cases. All patients exhibited large PDA and a patent foramen
ovale with increased right ventricle (RV) volume, and the myocardial
fibers were slightly congested and swollen. Pulmonary vessels showed
mild to moderate arterial media thickening. Lung hypoplasia and diffuse
lung damages reduced gas exchange, meanwhile the PDA and PH caused RV
failure, contributed a clinical picture of organ dysfunction, which lead
to death.
Conclusions: Pulmonary structures have certain heterogeneity in CDH. The
arteries’ pathological changes are not consistent with clinical
diagnosis. And the adverse outcome may should be due to the
cardiopulmonary vicious cycle.
Keyword: Congenital Diaphragmatic Hernia; Postmortem Examination;
Pulmonary Hypoplasia; Pulmonary Hypertension.
1.INTRODUCTION
Congenital diaphragmatic hernia
(CDH) is a serious life-threatening malformation, with an incidence of
per 2.3 in 10,000 births1, characterized by abdominal
visceral herniation into the chest. Infants with CDH are born with a
variable degrees of lung hypoplasia and abnormal pulmonary vasculature,
leading to ventilatory insufficiency and pulmonary hypertension
(PH)2. During the last decades, survival of CDH
patients has improved significantly due to the advances in neonatal
intensive care and minimally invasive surgery technologies, however
there are still 30-50% patients dying of fatal physiological
changes3. The optimal managements of severe CDH remain
challenging. Undoubtedly, severity of pulmonary hypoplasia, pulmonary
hypertension, and cardiac dysfunction are major determinants of CDH
outcome4, 5.
CDH can differ in size and location, the most common type are
posterolateral defects (Bochdalek hernia), presented in 70%-75% of
cases; Anterior defects (Morgagni hernia) present in 23%-28%; and
central hernias (2%-3%) are less frequent. Congenital eventration,
characterized by incomplete formation of the diaphragm musculature,
occurs in different parts of the diaphragm, and does not include
communication between the peritoneal and thoracic
cavities6,7. While diaphragm eventration is certainly
a less common phenotype of CDH which often misdiagnosed. Bochdalek
hernias occur mostly on the left side, however defects on the right side
and bilateral indicate a higher mortality8. The
pathogenesis of CDH is multifactorial and its epidemiology is poorly
understood9. Cardiopulmonary pathophysiological
processes in CDH patients are still ambiguous; in addition, the
permissions of autopsy have continued to decrease in recent decades, and
human tissue samples for translational and molecular studies of CDH are
rarely available10. Postmortem investigation helps to
identify the cause of death, as well as to explore the pathogenesis of
the disease based on human. Therefore, in this literature, we performed
few comprehensive autopsies of infants with CDH under the permission of
parents in our center, observed their pathological changes and clinical
characteristics, moreover, it is helpful to establish a biobank to
promote the translational study of CDH.
2.MATERIALS AND METHODS
Ethical approval (SHERLLM2022036) was obtained from the Health Research
Ethics Board of Children ’s Hospital, Capital Institute of Pediatrics.
Infants with CDH who were admitted to the intensive care unit between
2017 and 2022 July and died on initial admission at the Department of
Neonatal Surgery were included. With the informed consent of the
parents, a comprehensive autopsy was assessed by pediatric pathologists
in the Department of Pathology of our hospital. All bodies were placed
at 4 °C until the autopsy was performed and maximum time from death to
autopsy was 2 days postmortem. Paraffin blocks were retrieved from main
organs and tissues of the body, stained with hematoxylin and eosin (HE)
in 5μm thick sections, were also stained with antibodies against TTF-1
and alpha‐smooth muscle actin (HHF35) to better characterize pulmonary
epithelial cells and artery muscularization. The relevant clinical
diagnosis and treatment data derived from medical records were obtained.
The clinical data of CDH cases were retrospectively collected, including
gender, gestational age (GA) at diagnosis, GA in birth, birth weight
(BW), mode of delivery, side of hernia, liver herniation, defect size
(A, B, C, D) as used by the Congenital Diaphragmatic Hernia Study Group
(CDHSG) grade, and length of stay; disease-related information included
pulmonary hypertension (PH) (first cardiac ultrasound examination after
birth), cardiac anomalies; therapeutic interventions of PH, and repair
surgery.
3.RESULTS
The results of clinical data and autopsy reports with CDH are presented
in Table 1 and Table 2. Of the 8 patients (males=4, females=4), there
were 2(20%) cases of left diaphragmatic hernia, 5(62.5%) cases of
right and 1(12.5%) case misdiagnosed as left diaphragmatic hernia,
confirmed as bilateral congenital eventration at autopsy; 3 cases
(37.5%) of postoperative death and 5(62.5%) were failed to reach
preoperative steady state and died. The median GA at birth was 37.5
(range, 29-39, IQR 34.75-38.75) weeks and median GA in diagnosis was 22
(range, 22- 28, IQR 22-24.75) weeks; There were 7(87.5%) cesarean
sections and 1(12.5%) spontaneous delivery; the average birth weight
was 3006.25g ± 1017.85g; the average time of survive was 127.63h ±
205.62h (range, 8-624) h; defect size by CDHSG were divided into D
(57.1%)and C(42.9%), all of which had herniation of the liver
significantly. The degree of pulmonary hypertension was all recognized
as severe with a right-to-left shunt; Cardiac anomalies such as large
patent ductus arteriosus (PDA) and patent foramen ovale (PFO) were
diagnosed by echocardiography. After birth, 7 patients (85.7%) received
high-frequency ventilator-assisted ventilation (HFOV), with a median
initial mean airway pressure (MAP) of 14 (range, 14-22)
cmH2O and up to 18 (range, 16-22) cmH2O
finally. One received ECMO. Inotropic therapy was used to stabilize
blood pressure and maintain systemic pressure. All patients were treated
with vasoactive drugs including inhaled nitric oxide (iNO) and
Sildenafil.
Complications included left
ventricular (LV) dysplasia (1/8), pulmonary hemorrhage (3/8),
pneumothorax (3/8), scoliosis (1/8), and oliguria (2/8). Due to
persistent pulmonary hypertension of newborn (PPHN) at last, patients
died for severe refractory hypoxemia, cardiopulmonary failure,
uncorrectable decompensated mixed acidosis, and multiple organ failure.
Table 1. Demographics and characteristics of CDH Patients